NICHD Small Grants Programs--Perinatal HIV Transmission

NICHD 小额赠款计划——围产期艾滋病毒传播

• 批准号: 6653673
• 负责人: Felix O Aikhionbare
• 金额: $ 6.55万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6653673
• 关键词: HIV infections; clinical research; disease /disorder proneness /risk; embryo /fetus tissue /cell culture; gene mutation; genetic markers; genetic polymorphism; histocompatibility gene; human fetus tissue; human genetic material tag; human tissue; immunogenetics; immunopathology; linkage disequilibriums; major histocompatibility complex; molecular cloning; nucleic acid sequence; pediatric AIDS; polymerase chain reaction; single strand conformation polymorphism; statistics /biometry; vertical transmission

DESCRIPTION (provided by applicant): Perinatal transmission accounts for more than 90 percent of HIV-infection in children. A thorough understanding of the molecular and genetics mechanisms of the host immune gene response (such as chemokines, cytokines, HLA polymorphisms) effecting the pathogens and transmission consequences of host-HIV-1 interactions is essential to all aspects of public health for diagnostic, transmission, and prevention strategies. This study is designed to understand the mutational role of HLA-G gene that make HIV-1 infected women more (or less likely) to transmit virus to her infant. HLA-G is non-classical class 1 MHC gene and it is highly expressed in extravillous cytotrophoblast at the maternal fetal interface. Specific aim: To further examine the potential role (s) of the mutation in HLA-G exon 2, which was previously associated to reduced risk in perinatal transmission (Aikhionbare, AIDS 2001,15: 2196-8) and any mutation(s) in HLA-G untranslated region in DNA samples obtained from both Project RETRO-C1, 01 BP 1712, 10 Abidjan Cote d'Ivoire and Perinatal AIDS Collaborative Transmission Study (PACTS), for possibly increase or decrease in the susceptibility of a neonate to HIV-1- perinatal transmission. Approach: DNA samples will be obtained from HIV-1-infected and uninfected mother-child pairs followed as part of Project RETRO-C1, 01 BP 1712, 10 Abidjan Cote d'Ivoire and Perinatal AIDS Collaborative Transmission Study will be screened by the following techniques: WAVETM Nucleic Acid Fragment Analysis, allele-specific polymerase chain reaction (PCR), single strand conformational polymorphism (SSCP), followed by DNA cloning/sequencing. Molecular data from this study will be subjected to Fisher's exact test, Maximum likelihood, Linked disequilibrum parameter, Odd ratio, Relative risk analysis to groups value. Results will furnish new insights into the basic mechanisms of the viral pathogenesis in AIDS, especially the contribution of certain host genetic factors to HIV-1 perinatal infection.

描述(申请人提供)：围产期传播占儿童艾滋病毒感染的90%以上。深入了解宿主免疫基因反应(如趋化因子、细胞因子、人类白细胞抗原(HLA)多态性)影响宿主-HIV-1相互作用的病原体和传播后果的分子和遗传学机制，对于公共卫生的各个方面的诊断、传播和预防策略都是至关重要的。这项研究旨在了解人类白细胞抗原-G基因的突变作用，使感染HIV-1的妇女更有可能(或更不可能)将病毒传播给她的婴儿。人类白细胞抗原-G是一种非经典的1类MHC基因，在母胎界面绒毛外细胞滋养层细胞中高表达。具体目的：进一步研究人类白细胞抗原-G外显子2突变(S)和人类白细胞抗原-G非翻译区突变(S)在增加或降低新生儿对艾滋病毒-1-围产期传播的易感性方面的潜在作用。方法：从HIV-1感染和未感染的母婴配对中获取DNA样本，采用WAVETM核酸片段分析、等位基因特异性聚合酶链式反应(PCR)、单链构象多态性(SSCP)、DNA克隆/测序等技术，对科特迪瓦和围产期艾滋病协同传播研究进行筛查。本研究的分子数据将接受Fisher精确检验、最大似然检验、连锁不平衡参数、奇数比、相对风险分析。这一结果将为揭示艾滋病病毒致病的基本机制，特别是某些宿主遗传因素在HIV-1围产期感染中的作用提供新的思路。